Unconditional self-modifying code elimination with dynamic compiler optimizations

International audienceThis paper deals with the issue of self-modifying code and packed programs, a long-standing problem commonly addressed by emulation techniques and memory dumps. We propose an original semantics-based approach to simplify dynamic code analysis, by using compiler optimization techniques to get rid of code-generating instructions. For this, we use classic slicing techniques to identify code dependencies. As it is semantics-based, our approach allows us to rely on strongly established formal methods and is a promising approach for handling packed programs

B cell depletion in immune thrombocytopenia reveals splenic long-lived plasma cells.

International audiencePrimary immune thrombocytopenia (ITP) is a disorder caused by autoantibody-mediated platelet destruction and decreased platelet production. Rituximab, a B cell-depleting agent, has become the first-line treatment for ITP; however, patients with refractory disease usually require splenectomy. We identified antibody-secreting cells as the major splenic B cell population that is resistant to rituximab. The phenotype, antibody specificity, and gene expression profile of these cells were characterized and compared to those of antibody-secreting cells from untreated ITP spleens and from healthy tissues. Antiplatelet-specific plasma cells (PC) were detected in the spleens of patients with ITP up to 6 months after rituximab treatment, and the PC population displayed a long-lived program similar to the one of bone marrow PC, thus explaining for most of these patients the absence of response to rituximab and the response to splenectomy. When analyzed by multiplex PCR at the single-cell level, normal splenic PC showed a markedly different gene expression profile, with an intermediate signature, including genes characteristic of both long-lived PC and proliferating plasmablasts. Surprisingly, long-lived PC were not detected in untreated ITP spleens. These results suggest that the milieu generated by B cell depletion promotes the differentiation and settlement of long-lived PC in the spleen

Quantum Phase Transition in the SU(4) Spin-Orbital Model on the Triangular Lattice

Motivated by the absence of cooperative Jahn-Teller effect in LiNiO2 and BaVS3, two layered oxides with triangular planes, we study the SU(4) symmetric spin-orbital model on the triangular lattice. Upon reducing the next-nearest neighbour coupling, we show that the system undergoes a quantum phase transition to a liquid phase. A variational approach to this liquid phase shows that simple types of long-range correlations are suppressed, suggesting that it is stable against lattice distortions.Comment: 5 pages, 5 figures, RevTex

GPC3-Unc5 receptor complex structure and role in cell migration

Neural migration is a critical step during brain development that requires the interactions of cell-surface guidance receptors. Cancer cells often hijack these mechanisms to disseminate. Here, we reveal crystal structures of Uncoordinated-5 receptor D (Unc5D) in complex with morphogen receptor glypican-3 (GPC3), forming an octameric glycoprotein complex. In the complex, four Unc5D molecules pack into an antiparallel bundle, flanked by four GPC3 molecules. Central glycan-glycan interactions are formed by N-linked glycans emanating from GPC3 (N241 in human) and C-mannosylated tryptophans of the Unc5D thrombospondin-like domains. MD simulations, mass spectrometry and structure-based mutants validate the crystallographic data. Anti-GPC3 nanobodies enhance or weaken Unc5-GPC3 binding and, together with mutant proteins, show that Unc5/GPC3 guide migrating pyramidal neurons in the mouse cortex, and cancer cells in an embryonic xenograft neuroblastoma model. The results demonstrate a conserved structural mechanism of cell guidance, where finely balanced Unc5-GPC3 interactions regulate cell migration

The model of the adult attachment in the disturbance of the emotional regulation and the emotional links of the hospitalized women suffering from depression

Notre recherche a pour objectif de montrer que le modèle de l’attachement adulte constitue un facteur de vulnérabilité psychologique explicatif de la dépression des femmes et de son évolution sur deux aspects : la perturbation de la régulation émotionnelle (stratégies d’attachement) et l’insécurité des représentations des liens d’attachement passés (expériences parentales) et actuels (styles d’attachement amoureux et interpersonnel). Il s’agit de déterminer aussi les liens existants entre la personnalité des femmes déprimées et l’attachement adulte. Nous portons un intérêt plus spécifique à l’évolution des liens entre la dépression et les styles d’attachement (stabilité ou modification) durant l’hospitalisation. Les résultats principaux de notre étude indiquent des liens significatifs entre la dépression et l’insécurité des stratégies (à dominance préoccupée), des représentations des expériences passées (préoccupée et non résolues) et des styles d’attachement (à dominance craintive) amoureux et interpersonnel. Quant aux femmes déprimées ayant un trouble de personnalité, elles sont davantage préoccupées dans les représentations des relations actuelles. Enfin, les résultats montrent que seul le style d’attachement interpersonnel secure se modifie en fonction de la diminution de la dépression durant l’hospitalisation tandis que l’ensemble des styles d’attachement amoureux reste stable. Ces résultats permettent de mettre en évidence des caractéristiques psychopathologiques spécifiques chez les femmes déprimées concernant la perturbation de la régulation émotionnelle (hyper-activation des affects en lien avec les « troubles psychopathologiques internalisés », stratégies défensives de détachement, difficultés de mentalisation) et les représentations insécurisées des liens d’attachement passés (focalisation excessive sur les relations parentales, ambivalence, dépendance, expériences traumatiques) et présents (anxiété affective et relationnelle mais défiance par peur d’être rejetée). L’étude de l’attachement permet d’apporter des éléments de compréhension sur le lien insecure à l’autre chez les femmes déprimées présentant une personnalité pathologique. Nous discutons également des rapports entre la vulnérabilité dépressive et la stabilité ou la modification des styles d’attachement. Enfin, nous évoquons les perspectives thérapeutiques (notamment le travail sur la mentalisation) de l’étude et les limitesThe purpose of our research is to show that the model of adult attachment constitute a factor of psychological vulnerability that explain women depression and its evolution on two levels: the disturbance of the emotional regulation (attachment strategies) and the insecurity of the representation of the past links of attachment (parental experiences), and the current ones (love and interpersonal attachment). The aim is also to determine the existing links between the personality of the depressed women and adult attachment. We have a more interest more specific in the study of the evolution between the depression and the patterns of attachment (stability or alteration) during hospitalization. The main results of our study show significant links between the depression and the insecurity of attachment strategies (mainly preoccupied), representations of the past experiences (preoccupied and unresolved) and love and interpersonal attachment styles (mainly fearful). As regards to depressed women suffering from a personality disorder, they are more preoccupied in the representations of the current attachment relations. At least; the results show than only interpersonal attachment styles modified according to the decrease of the depression during hospitalization, while all loving attachment styles remain stable.These results obviously allow to specific psychopathological characteristics in depressed women concerning the disturbance of the emotional regulation (hyper-activation of the affects, linked with internalizing psychopathological disorders, defensive strategies of detachment, and difficulties of mentalization) and the insecure representations of the past links of attachment (excessive focus of the parental relations, ambivalence, dependence, traumatic experiences) and present (relational and affective anxiety, but mistrust for fearof being rejected). The study of the attachment allows us to bring comprehensive elements about the insecure relationship to the other in the depressed women with a pathological personality. We also discuss about links between depressive vulnerability and stability or the modification of the attachment styles. At least we evoke the therapeutic perspectives (in particular the work of the mentalization) of the study and the limits

Le modèle de l'attachement adulte dans la perturbation de la régulation émotionnelle et des liens affectifs des femmes hospitalisées souffrant de dépression

The purpose of our research is to show that the model of adult attachment constitute a factor of psychological vulnerability that explain women depression and its evolution on two levels: the disturbance of the emotional regulation (attachment strategies) and the insecurity of the representation of the past links of attachment (parental experiences), and the current ones (love and interpersonal attachment). The aim is also to determine the existing links between the personality of the depressed women and adult attachment. We have a more interest more specific in the study of the evolution between the depression and the patterns of attachment (stability or alteration) during hospitalization. The main results of our study show significant links between the depression and the insecurity of attachment strategies (mainly preoccupied), representations of the past experiences (preoccupied and unresolved) and love and interpersonal attachment styles (mainly fearful). As regards to depressed women suffering from a personality disorder, they are more preoccupied in the representations of the current attachment relations. At least; the results show than only interpersonal attachment styles modified according to the decrease of the depression during hospitalization, while all loving attachment styles remain stable.These results obviously allow to specific psychopathological characteristics in depressed women concerning the disturbance of the emotional regulation (hyper-activation of the affects, linked with internalizing psychopathological disorders, defensive strategies of detachment, and difficulties of mentalization) and the insecure representations of the past links of attachment (excessive focus of the parental relations, ambivalence, dependence, traumatic experiences) and present (relational and affective anxiety, but mistrust for fearof being rejected). The study of the attachment allows us to bring comprehensive elements about the insecure relationship to the other in the depressed women with a pathological personality. We also discuss about links between depressive vulnerability and stability or the modification of the attachment styles. At least we evoke the therapeutic perspectives (in particular the work of the mentalization) of the study and the limits.Notre recherche a pour objectif de montrer que le modèle de l’attachement adulte constitue un facteur de vulnérabilité psychologique explicatif de la dépression des femmes et de son évolution sur deux aspects : la perturbation de la régulation émotionnelle (stratégies d’attachement) et l’insécurité des représentations des liens d’attachement passés (expériences parentales) et actuels (styles d’attachement amoureux et interpersonnel). Il s’agit de déterminer aussi les liens existants entre la personnalité des femmes déprimées et l’attachement adulte. Nous portons un intérêt plus spécifique à l’évolution des liens entre la dépression et les styles d’attachement (stabilité ou modification) durant l’hospitalisation. Les résultats principaux de notre étude indiquent des liens significatifs entre la dépression et l’insécurité des stratégies (à dominance préoccupée), des représentations des expériences passées (préoccupée et non résolues) et des styles d’attachement (à dominance craintive) amoureux et interpersonnel. Quant aux femmes déprimées ayant un trouble de personnalité, elles sont davantage préoccupées dans les représentations des relations actuelles. Enfin, les résultats montrent que seul le style d’attachement interpersonnel secure se modifie en fonction de la diminution de la dépression durant l’hospitalisation tandis que l’ensemble des styles d’attachement amoureux reste stable. Ces résultats permettent de mettre en évidence des caractéristiques psychopathologiques spécifiques chez les femmes déprimées concernant la perturbation de la régulation émotionnelle (hyper-activation des affects en lien avec les « troubles psychopathologiques internalisés », stratégies défensives de détachement, difficultés de mentalisation) et les représentations insécurisées des liens d’attachement passés (focalisation excessive sur les relations parentales, ambivalence, dépendance, expériences traumatiques) et présents (anxiété affective et relationnelle mais défiance par peur d’être rejetée). L’étude de l’attachement permet d’apporter des éléments de compréhension sur le lien insecure à l’autre chez les femmes déprimées présentant une personnalité pathologique. Nous discutons également des rapports entre la vulnérabilité dépressive et la stabilité ou la modification des styles d’attachement. Enfin, nous évoquons les perspectives thérapeutiques (notamment le travail sur la mentalisation) de l’étude et les limite

Family wise separation rates for multiple testing

to appear in Annals of StatisticsInternational audienceStarting from a parallel between some minimax adaptive tests of a single null hypothesis, based on aggregation approaches, and some tests of multiple hypotheses, we propose a new second kind error-related evaluation criterion, as the core of an emergent minimax theory for multiple tests. Aggregation-based tests are justified through their first kind error rate, which is controlled by the prescribed level on the one hand, and through their separation rates over various classes of alternatives, rates that are minimax on the other hand. We show that these tests can be viewed as the first steps of classical step-down multiple testing procedures, and ac-cordingly be evaluated from the multiple testing point of view also, through a control of their Family-Wise Error Rate (FWER). Conversely, many multiple testing procedures, from the historical ones of Bonferroni and Holm, to more recent ones like min-p procedures or randomized procedures, can be investigated from the minimax adaptive testing point of view. To this end, we extend the notion of separation rate to the multiple testing field, by defining the weak Family-Wise Separation Rate and its stronger counterpart, the Family-Wise Separation Rate (FWSR). As for non-parametric tests of a single null hypothesis, we prove that these new concepts allow an accurate analysis of the second kind error of a multiple testing procedure, leading to clear definitions of minimax and minimax adaptive multiple tests. Some illustrations in a classical Gaussian framework corroborate several expected results under particular conditions on the tested hypotheses, but also lead to more surprising results

Optimal Change-Point Detection and Localization

International audienceGiven a times series Y in R n , with a piece-wise contant mean and independent components, the twin problems of change-point detection and change-point localization respectively amount to detecting the existence of times where the mean varies and estimating the positions of those change-points. In this work, we tightly characterize optimal rates for both problems and uncover the phase transition phenomenon from a global testing problem to a local estimation problem. Introducing a suitable definition of the energy of a change-point, we first establish in the single change-point setting that the optimal detection threshold is 2 log log(n). When the energy is just above the detection threshold, then the problem of localizing the change-point becomes purely parametric: it only depends on the difference in means and not on the position of the change-point anymore. Interestingly, for most change-point positions, including all those away from the endpoints of the time series, it is possible to detect and localize them at a much smaller energy level. In the multiple change-point setting, we establish the energy detection threshold and show similarly that the optimal localization error of a specific change-point becomes purely parametric. Along the way, tight optimal rates for Hausdorff and l 1 estimation losses of the vector of all change-points positions are also established. Two procedures achieving these optimal rates are introduced. The first one is a least-squares estimator with a new multiscale penalty that favours well spread change-points. The second one is a two-step multiscale post-processing procedure whose computational complexity can be as low as O(n log(n)). Notably, these two procedures accommodate with the presence of possibly many low-energy and therefore undetectable change-points and are still able to detect and localize high-energy change-points even with the presence of those nuisance parameters

Kernels based tests with non-asymptotic bootstrap approaches for two-sample problem

International audienceConsidering either two independent i.i.d. samples, or two independent samples generated from a heteroscedastic regression model, or two independent Poisson processes, we address the question of testing equality of their respective distributions. We first propose single testing procedures based on a general symmetric kernel. The corresponding critical values are chosen from a wild or permutation bootstrap approach, and the obtained tests are exactly (and not just asymptotically) of level . We then introduce an aggregation method, which enables to overcome the difficulty of choosing a kernel and/or the parameters of the kernel. We derive non-asymptotic properties for the aggregated tests, proving that they may be optimal in a classical statistical sense